The present invention generally relates to gas chromatography, and specifically, to parallel gas chromatograph systems that can be integrated or used with parallel reactors for high-throughput (i.e., combinatorial) catalyst screening. The present invention also generally relates to microdetectors, and specifically, to microfabricated thermal conductivity detectors suitable for use in gas chromatography, flow detection, catalyst characterization, and other applications. The invention particularly relates, in a preferred embodiment, to parallel gas chromatograph systems with an array of microdetectors, such as microfabricated thermal conductivity detectors.
Gas chromatography, and in particular, multi-channel gas chromatography is known in the art. See, for example, PCT patent application WO 00/23734 (Daniel Industries, Inc.). Thermal conductivity detectors are also known in the art, and have been routinely used for detection in gas chromatographsxe2x80x94alone, or in combination with other detectors. See, for example, U.S. Pat. No. 4,594,879 to Maeda et al., and Great Britain Patent Specification GB 1,262,529.
Combinatorial (i.e., high-throughput) catalysis is likewise known in the art. See U.S. Pat. No. 5,985,356 to Schultz et al., U.S. Pat. No. 6,004,617 to Schultz et al., U.S. Pat. No. 6,030,917 to Weinberg et al., U.S. Pat. No. 5,959,297 to Weinberg et al., U.S. Pat. No. 6,063,633 to Wilson, U.S. Pat. No. 6,149,882 to Guan et al., and PCT applications WO 99/64160, WO 99/51980, WO 00/09255, WO 00/23921, WO 00/32308 and WO 00/51720 each of which patents and applications relates to various aspects of combinatorial materials science and combinatorial catalysis, and each of which (including corresponding US applications from which priority is claimed) is hereby incorporated by reference for all purposes.
Despite the considerable development in the art of gas chromatography to date, there remains a need for improved gas chromatographs to facilitate, among other applications, high-throughput screening of catalysts in parallel fashionxe2x80x94with simultaneous injection, separation and/or detection in multiple analysis channels. In particular, the current state of the art suffers from relatively bulky packaging, limited interchangeability of component parts, limited operational flexibilty and considerable manufacturing expense. Moreover, existing gas chromatographs are not readily integrated into reaction systems, and especially into smaller-scale reactors such as microreactors, for catalyst screening and/or process optimization.
It is therefore an object of the present invention to provide improved gas chromatographs and improved microdetectors for parallel gas chromatography that overcome the deficiencies of the prior art. Specifically, it is an object of the invention to provide a gas chromatograph that is more spatially efficient, provides more operational flexibility, and is more economical to manufacture. It is also an object of the invention to provide gas chromatograph that is suitable for applications with high-throughput screening (e.g. of catalysts), including screening of catalysts using parallel flow reactors or parallel flow microreactors.
Briefly, therefore, included among the several inventions disclosed herein, are arrays of microdetectors, especially thermal conductivity microdetectors, parallel gas chromatographs comprising such microdetector arrays, and parallel catalyst evaluation systems comprising parallel reactors integrated with such parallel gas chromatographs. The present invention also includes highly parallel gas chromatograph systems (e.g. having more than about 8 channels, and preferably more than about 16 channels) having improved thermal control. Additional inventions, including parallel injection blocks (for simultaneous injection and simultaneous vaporization of liquid samples), independently and collectively with parallel injection valves (for parallel injection of gaseous samples to gas chromatography columns) are also disclosed. Inventive methodologies are likewise disclosed herein, including for example, methods for parallel gas chromatography, methods for evaluating libraries of catalyst candidates using such gas chromatography methods, methods for parallel detection of thermal conductivity, and methods for detecting improper injections to gas chromatograph systems.
More specifically, the present invention is directed to a gas chromatograph having four or more analysis channels for simultaneous analysis of four or more fluid samples. The gas chromatograph comprises four or more gas chromatography columns (each comprising an inlet for receiving a gaseous mobile phase that includes a gaseous sample, a separation media effective for separating at least one separated component of the gaseous sample from other components thereof, and an outlet for discharging the separated gaseous sample) and a microdetector array comprising four or more thermal conductivity microdetectors for detecting the thermal conductivity of said at least one separated component of the gaseous sample, said thermal conductivity microdetectors being integral with a substrate or mounted on the substrate. The four or more thermal conductivity microdetectors generally have an inlet port in fluid communication with the outlet of one or more of the gas chromatography columns for receiving a separated gaseous sample, a detection cavity, a thin-film detection filament within the detection cavity for detecting at least one separated component of the separated gaseous sample, and an outlet port for discharging the separated gaseous sample.
The gas chromatographs of the present invention include several variously characterized embodiments. The microdetectors are, in one embodiment, preferably microfabricated microdetectors that are integral with the substrate or with one or more microchip bodies mounted on the substrate. In another embodiment, the microdetectors are thermal conductivity detectors comprising a thin-film detection filament in the detection cavity, where the detection filament has a temperature-dependent resistance. In additional embodiments described in greater detail hereinafter, the microdetectors are bonded to the substrate, or are alternatively detachably mounted on the substrate, preferably as microchip bodies comprising one or more microdetectors
In a particularly preferred embodiment, the gas chromatograph is a six-channel gas chromatograph for simultaneous analysis of six or more fluid samples. The gas chromatograph can comprise six or more gas chromatography columns (each of the six or more gas chromatography columns comprising an inlet for receiving a gaseous mobile phase that includes a gaseous sample, a separation media effective for separating at least one component of the sample from other components thereof, and an outlet for discharging the mobile phase and the separated sample) and a microdetector array comprising six or more sample thermal conductivity detectors and at least one reference thermal conductivity detector. Each of the sample and reference thermal conductivity detectors are integral with or mounted on a substrate with a planar density of at least about 1 thermal conductivity detector per 1 cm2, and the ratio of sample detectors to reference detector(s) is at least 2:1. Each of the six or more sample thermal conductivity detectors comprises an inlet port in fluid communication with the outlet of one of the gas chromatography columns for receiving a separated sample, a detection cavity having a volume ranging from about 1 xcexcl to about 500 xcexcl for detecting at least one component of the separated sample, a thin-film detection filament within the detection cavity, the detection filament having a temperature-dependent resistance, an outlet port for discharging the sample, a first conductive path between the a first end of the detection filament and a first electrical contact, and a second conductive path between a second end of the detection filament and a second electrical contact. The first and second electrical contacts are adapted for electrical communication with one or more integral or external signal-processing circuits. The at least one reference thermal conductivity detector has an inlet port in fluid communication with a reference gas source for receiving a reference gas, a detection cavity comprising a thin-film detection filament within the detection cavity for detecting the reference gas, and an outlet port for discharging the detected reference gas. The six or more sample thermal conductivity detectors each have a thermal coefficient of resistance that varies less than about 10% between the six or more thermal conductivity detectors.
The invention is likewise directed to an integrated apparatus comprising a gas chromatograph as set forth (including variations and specific attributes as described or claimed hereinafter), and a parallel flow reactor having four or more reaction vessels. Each of the four or more reaction vessels comprises an inlet for feeding reactants into the reaction vessel, a reaction zone for effecting a chemical reaction, and an outlet for discharging reaction products and unreacted reactants, if any. The outlets of the four or more reaction vessels can be in at least sampling fluid communication with the inlets of the four or more gas chromatography columns, respectively. The parallel flow reactors can be typical bench scale, or smaller scale, such as massively-parallel microreactors (e.g., as described in WO 00/51720) or intermediate scale parallel-flow reactors (e.g., such as the parallel fixed bed reactors as described in U.S. Pat. No. 6,149,882 to Guan et al., commercially available from Zeton Altamira (Pittsburgh, Pa.) and, with higher numbers of reaction channels, from Symyx Technolgies, Inc. (Santa Clara, Calif.).
The invention is further directed to a microdetector array comprising four or more thermal conductivity detectors. The four or more thermal conductivity detectors are integral with or mounted on a substrate with a planar density of at least about 1 thermal conductivity detector per 10 cm2. Each of the thermal conductivity detectors comprise a detection cavity having a volume of not more than about 500 xcexcl, an inlet port for admitting a fluid sample into the detection cavity, one or more thin-film detection filaments within the detection cavity, the detection filament having a temperature-dependent resistance, an outlet port for discharging a fluid sample from the detection cavity, first and second electrical contacts for electrical communication with a signal-processing circuit, a first conductive path between the first electrical contact and a first end of the detection filament, and a second conductive path between the second electrical contact and a second end of the detection filament. In preferred embodiments, the microdetectors are mounted on the substrate, individually or as modules, by being bonded to the substrate, or by being detachably mounted on the substrate, in either case, preferably as microchip bodies comprising one or more of the thermal conductivity microdetectors.
The invention is directed, moreover, to a method for parallel analysis of four or more fluid samples by gas chromatography. The method comprises injecting four or more gaseous samples into respective mobile phases of four or more gas chromatography columns, contacting the four or more gaseous samples with separation media in the respective gas chromatography columns to separate at least one component of the sample (i.e., one analyte) from other constituents of the gaseous samples, and detecting the four or more separated analytes with a microdetector array comprising four or more microdetectors. The array of microdetectors are preferably microfabricated microdetectors (e.g., TCD""s). The array preferably comprises four or more thermal conductivity detectors having one or more thin-film detection filaments in the detection cavity. In preferred embodiments, the array comprises microdetectors integral with or mounted on the substrate. The microdetectors can be mounted, individually or as modules, by being bonded to the substrate, or by being detachably mounted on the substrate, in either case, preferably as microchip bodies comprising one or more of the thermal conductivity microdetectors.
The invention is also directed to a gas chromatograph, and methods of using the same, where the gas chromatograph has larger numbers of analysis channelsxe2x80x94especially to systems having eight or more, and preferably sixteen or more, twenty-four or more, forty-eight or more or ninety-six or more gas chromatography columns adapted for simultaneous analysis of a like number of samples (e.g. such as are generated in a combinatorial catalysis experiment). Specifically, the gas chromatograph comprises eight or more gas chromatography columns residing in a heated environment, and a detector array comprising eight or more detectors (i.e. at least eight detection channels, whether in a single instrument, such as the preferred microdetector array described above, or in separate conventional detection instruments). Each of the of the eight or more gas chromatography columns have an inlet for receiving a gaseous mobile phase that includes a gaseous sample, a separation media effective for separating at least one component of the sample from other components thereof, and an outlet for discharging the separated sample. The heated environment is adapted to provide substantially the same temperature profile, temporally, for the eight or more gas chromatography columnsxe2x80x94as measured at substantially the same spatial location on each column at a given time during a temperature excursion of at least about 10xc2x0 C. In particular, the temperature of the eight or more columns is preferably substantially the samexe2x80x94as measured as such, and preferably does not vary by more than about 10xc2x0 C., preferably not more than about 5xc2x0 C., 2xc2x0 C., 1xc2x0 C., 0.5xc2x0, and 0.1xc2x0 C., as measured as such. Additionally or alternatively, the heated environment provides a substantially uniform time-rate-of-change in temperature to each of the eight or more gas chromatography columns (e.g., during a temperature ramping excursion)xe2x80x94as measured at a given time during a temperature excursion at substantially the same spatial location of the compared columns. Preferably, the rate of change in temperature varies by not more than about 10%, and preferably not more than about 5%, 2%, 1%, or 0.5% as measured as such. In a particularly preferred embodiment, the heated environment comprises a convection zone for directed flow of a fluid in a substantially uniform direction past the eight or more gas chromatography columns. In any case, the eight or more detectors each have an inlet port in fluid communication with the outlet of one or more of the gas chromatography columns for receiving a separated sample, a detection cavity for detecting at least one component of the separated sample, and an outlet port for discharging the sample.
The invention is additionally directed to methods for evaluating the catalytic performance of candidate catalysts. Four or more candidate catalysts are simultaneously contacted with one or more reactants in a parallel reactor under reaction conditions to catalyze at least one reaction, and the resulting reaction products or unreacted reactants are detected in parallel with the gas chromatographs of the invention, as described or claimed herein, to determine the relative performance of the candidate catalysts. The candidate catalysts can be the same or different between reaction channels, and the reaction conditions (e.g., temperature, pressure, feed flowrate, residence time, feed composition) can likewise be the same or different between reaction channels.
The parallel detection systems of the present invention are of substantial importance for high-throughput combinatorial catalysis research programs. Parallel screening reactors, such as flow reactors as disclosed in U.S. Ser. No. 09/093,870 filed Jun. 9, 1998 by Guan et al. (herein xe2x80x9c98-13xe2x80x9d, and now issued as U.S. Pat. No. 6,149,882), U.S. Ser. No. 09/518,794 filed Mar. 3, 2000 by Bergh et al. (herein xe2x80x9c99-1xe2x80x9d), U.S. Ser. No. 60/185,566 filed Mar. 7, 2000 by Bergh et al. (herein xe2x80x9c00-022xe2x80x9d), U.S. Ser. No. 09/801,390, entitled xe2x80x9cParallel Flow Process Optimization Reactorsxe2x80x9d filed on the date even herewith (Mar. 7, 2001) by Bergh et al., U.S. Ser. No. 09/801,389, entitled xe2x80x9cParallel Flow Reactor Having Variable Compositionxe2x80x9d filed on the date even herewith (Mar. 8, 2001) by Bergh et al., and U.S. Serial No. 60/274,065, entitled xe2x80x9cParallel Flow Reactor Having Improved Thermal Controlxe2x80x9d filed on the date even herewith (Mar. 7, 2001) by Bergh et al. can effect reactions in tens, hundreds or even thousands of channels simultaneously or substantially concurrently. Parallel detection systems, such as two-channel gas chromatography systems, have been advantageously applied in connection with some such parallel reaction systems, but are inherently limited by their size (bulk) and, significantly, by their cost per channel.
The parallel detection systems disclosed herein, comprising a microdetector array, overcome the substantial cost and space constraints of conventional gas chromatographs. The gas chromatographs of the present invention also offer significant improvements with respect to modularity and interchangeability of components, and especially of the detectors. Significantly, the microfabricated microdetectors can be economically manufactured using conventional microfabrication techniques, allowing for improved manufacturing approaches. Microfabrication also provides reproducible, advantageous performance characteristics, especially when applied in connection with forming thin-film detection filaments. The detection systems disclosed herein also provide improvements in sample-handling efficiency and, as such, improve overall sample throughput for a catalysis research program.
The apparatus and methods are disclosed herein primarily in the context of gas chromatography, and particularly in connection with combinatorial catalysis research programs. The inventions are broadly useful in such programs, including for example, heterogeneous catalysis and homogeneous catalysis, as applied in commodity chemicals, fine chemicals, and/or specialty chemicals, with flow, semi-continuous, and/or batch reactor systems.
The apparatus are also useful, however, in other applications. For example, other applications for the parallel thermal conductivity array are contemplated, including parallel flow sensing (e.g. parallel flow anemometers), and parallel catalyst characterization (e.g., using parallel temperature-programmed desorption, parallel temperature-programmed reduction, and/or parallel temperature-programmed oxidation protocols). The parallel detection apparatus (i.e., gas chromatographs and/or microdetector arrays) and methods can also be employed in connection with environmental sensing, process monitoring, process control, defense, first-responder and other applications. In some applications, the parallel gas chromatograph and associated methods can be applied to evaluation of chromatography media for gas chromatography columns (e.g. having a different media in each column, injecting the same sample into each of the columns and comparing the detected separation effect). Additional applications will be apparent to those of skill in the art.
Other features, objects and advantages of the present invention will be in part apparent to those skilled in art and in part pointed out hereinafter. All references cited in the instant specification are incorporated by reference for all purposes. Moreover, as the patent and non-patent literature relating to the subject matter disclosed and/or claimed herein is substantial, many relevant references are available to a skilled artisan that will provide further instruction with respect to such subject matter.